Process-induced mechanical stress is used to enhance carrier transport and achieve higher drive currents in current complementary metal-oxide-semiconductor technologies. This paper explores how to fully exploit the layout dependence of stress enhancement and proposes a circuit-level, block-based, stress-enhanced optimization algorithm that uses stress-optimized layouts in conjunction with dual- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> assignment to achieve optimal power-performance tradeoffs. We begin by studying how channel stress and drive current depend on layout parameters such as active area length and contact placement, while considering all layout-dependent sources of mechanical stress in a 65 nm industrial process. We then investigate the three main layout properties that impact mechanical stress in this process and discuss how to improve stress-based performance enhancement in standard cell libraries. While varying the stress-altering layout properties of a number of standard cells in a 65 nm industrial library, we show that ?dual-stress? standard cell layouts (analogous to ?dual- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> ?) can be designed to achieve drive current differences up to ~ 14% while incurring less than half the leakage penalty of dual- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> . Therefore, when the flexibility of ?dual-stress? assignment is combined with dual- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> assignment (within the proposed joint optimization framework), simulation results for a set of benchmark circuits show that leakage is reduced by ~ 24% on average, for iso-delay, when compared to dual- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> assignment. Since mobility enhancement does not incur the exponential leakage penalty associated with <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">V</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> assignment, our optimization technique is ideal for leakage power reduction. However, our framework can also be used to achieve higher performance circuits for iso-leakage and our joint optimization framework can be used to reduce delay on average by ~ 5%. In both cases, the proposed method only incurs a small area penalty (<0.5%).